Induction therapy with pemetrexed/platinum followed by maintenance with pemetrexed is a standard chemotherapy regimen in the frontline setting in patients with NSCLC harboring no sensitizing EGFR mutations. In this patient population, no survival benefit has been observed with gefitinib monotherapy or with platinum-based doublet chemotherapy.a The GENIUS trial was a prospective, randomized, phase 2 open-label trial comparing maintenance gefinitib+pemetrexed (G/P) versus pemetrexed (P) alone in patients with metastatic lung adenocarcinoma (MLADC) harboring no sensitizing EGFR mutations (sEGFRm), following a 4-cycle P/platinum induction therapy in the frontline setting.b Patients with no disease progression (PD) after induction therapy were randomized 1:1 to receive maintenance P (500 mg/m2, 3-week cycle) ± G (250 mg, daily) until PD or treatment failure. The primary endpoint was progression free survival (PFS) by both independent radiologist review (IRR) and investigator assessment (IA); secondary endpoints included time to treatment failure (TTF), overall survival (OS), safety, and toxicity profile.
A total of 55 patients were randomized on this study (G/P=26, P=29) for IA and 52 for IRR (G/P=25, P=27). Median PFS was substantially longer for G/P than P, both by IRR: 8.4 vs. 3.8 months (HR [95% CI]=0.35 [0.18-0.68]; P = 0.0039), and by IA: 8.7 vs. 2.9 months (HR 0.34 [0.18-0.64], P = 0.0009). Median TTF was 7.0 versus 2.9 months (HR 0.43 [0.24-0.79], P = 0.082) for G/P versus P, respectively. There was more treatment-related diarrhea, liver, and skin toxicities on G/P versus P, but all adverse events were generally mild. Death occurred in 8 G/P patients and in 14 P patients. The authors concluded that GENIUS is the first prospective trial to show robust PFS benefit of gefitinib plus pemetrexed in the maintenance phase after first-line treatment for MLADC with no sEGFRm. This strategy requires a phase 3 study to confirm.
